SUN-015 - Pituitary Cushing'S Disease without Cardinal Features in A Thin-Phenotype Polycystic Ovarian Syndrome Patient: A Biochemical Approach

Introduction: There is a wide phenotypic presentation of polycystic-ovarian-syndrome (PCOS), with many patients falling into a metabolic/obese phenotype at high diabetes risk or a lean phenotype with higher adrenal hyperandrogenism, especially increased dehydroepiandrostendione-sulfate (DHEAS) [1]. We describe a patient with lean-phenotype PCOS and normal thyroid function who lacked classic cushingoid features but was diagnosed with pituitary Cushing’s disease (CD) through biochemical evaluation.

Case Report: A 33-year-old female (Body-mass-index 22) was initially referred for suspected thyroid disease; thyroid function and antibodies were normal. She had irregular menses and acne. Initial labs: DHEAS 537 μg/dL Upper-limit-normal (ULN 373), total testosterone (TT) 34 ng/dL (ULN 60), free testosterone (FT) 2.0 pg/mL (ULN 4.2). She was managed as lean-PCOS with oral contraceptives and spironolactone. One year later she returned with bloating and nausea while on a Mirena intrauterine-device, spironolactone, and metformin. Repeat labs showed DHEAS 667 µg/dL, TT 49 ng/dL, FT 5.9 pg/mL. CT-abdomen showed mild left adrenal nodularity. A 2 day dose dexamethasone suppression test (2DDST), partially suppressed DHEAS to 373 µg/dL, with cortisol 7.3 µg/dL and Adrenal-Corticotropin-Hormone ( ACTH) 18 pg/mL. Incomplete cortisol suppression prompted hypercortisolism workup. Multiple subsequent tests results showed midnight-salivary-cortisol (MSC) 0.99 and 0.18 µg/dL; 24-h urinary free cortisol (UFC) 194 and 195 µg/24h; 1-mg desamethasonesuppression test (LDST), cortisol 20.4 µg/dL (dex 126 ng/dL, ACTH 18.6 pg/mL); random AM cortisol 22.3 µg/dL (ACTH 21.7), confirming biochemical hypercortisolism. High suspicion for a central source prompted pituitary MRI, showed a 4 × 6 mm microadenoma. Despite absent Cushingoid features, Intra-petrosal-sulcus-sampling (IPSS) confirmed a central ACTH source. She underwent transsphenoidal-resection; pathology showed a corticotrophin-adenoma. Postoperative cortisol 2.0 µg/dL and ACTH 6.6 pg/mL indicated remission.

Discussion: Pituitary CD may present subtly in lean-phenotype PCOS, where elevated DHEAS can be attributed to PCOS rather than hypercortisolism. Sequential biochemical assessment—including LDSTs, MSC and UFC, and IPSS—was essential for diagnosis. Mild asymmetric adrenal enlargement may occur in pituitary CD.

Conclusion: This case underscores the need for a biochemical-centered approach when hyperandrogenism coexists with nonspecific symptoms, as phenotype alone may lead to missed or delayed diagnosis of pituitary CD.
Reference: 1. Thota-Kammili S, Kolagatla S, Uy EM, et al. PCOS diagnosis leading to a delayed diagnosis of Cushing’s disease. Endocr Pract. 2023;29(Suppl 1):S87. Abstract #1405095. doi:10.1016/j.eprac.2023.03.195.

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